Mfm 2 Exam 2 Alley/bassett

Front 1

problems with phagocytes, complement, Nk cells lead to what?

Back 1

phagocytes - extracellular bacteria/fungi
Complement - extracellular bacteria especially neisseria
NK cells - herpes infections

Front 2

X - linked SCID

Back 2

T-, B+, NK-; MOST COMMON in Males; X-linked;
mutation gamma subunit IL receptor for:
IL2 (lymphocyte proliferation), IL4 (Bcell ), IL7 (TCR rearrangement), IL9 (Loss anti-apoptotic signal in thymus), IL15 (ablation NK cells)
Sx: recurrent infections of 3 mo (no more IgG from mom), failure to thrive, fevers, dehydration, no lymphadenopathy

Front 3

JAK 3 deficiency

Back 3

auto recessive SCID
same phenotype as X-linked; T-,B+,NK-
JAK/STAT = cytokine signaling receptor
JAK3 is a protein tryosine kinase assoc. with gamma chain of ILR's

Front 4

ADA and PNP deficiency

Back 4

auto recessive SCIDs
ADA - Adenosine deaminase deficiency = T-,B-,NK-; build up of toxic metabolites which block T, B, NK cell
PNP - purine nucleoside phosphorylase deficiency = T-,B+,NK- = increase of dATP, dGTP = thymocyte destruction
Sx: Recurrent viral, bacterial, fungal, mycobacterial, protozoal infections + neuro deficits

Front 5

RAG1/RAG2 deficiencies

Back 5

auto recessive SCID
No rearrangement/somatic recombination of hypervariable regions = reduced/absent T/B cell function and reduction in #
reduced/absent immunoglobulin Levels
decreased amount of antigens recognized

Front 6

Wiskott - Aldrich Syndrome

Back 6

defect in Wasp protein - small G-protein in actin skeleton reorginization => immune synapse problems b/w T and B cells during activation. lack of functional T helper cells.
Sx: growth deficits, skin (eczema, purpura) infectoins of head, neck, pulmonary; high malignancies, neurological problems
problems with encapsulated organisms
Tx: bone marrow transplant

Front 7

DiGeorge syndrome

Back 7

thymus absent => defective Tcells b/c of 22q11.21 through 22q11.23 deletion
Sx: recurrent infections from birth, facial features -> hyperteloris, micrognathia, fish-mouth, low set ears, low chin; parathyroid problems -> low calcium

Front 8

Bare lymphocyte

Back 8

Tcell problems
MHC1 def - T-,B+,NK+; defect in TAP gene = no HLA1's and no CD8 Tcells = no CTL's
MHC2 def: T-,B+,NK+; transcriptional regulators of HLA2's defect; selective loss of CD4 T celss

Front 9

X-linked agammaglobulinemia - BRUTONS

Back 9

X-linked = males; No production of IgG
defect in protein kinase btk gene -> no develop past Pre-B cell so no IgM
Extracellular pathogens

Front 10

X-linked Hyper IgM syndrome

Back 10

X-linked = males
high IgM count => no isotype switching
CD40L mutation => cant activate APCs and no Bcell activation.
Sx: pyogenic bacterial infections; low Ig counts

Front 11

Selective IgA deficieny

Back 11

MOST COMMON - 80% of immunodeficiencies
decreased/absent IgA -> mucosa, resp, gi,
2nd and 3rd generation of life

Front 12

ELISA

Back 12

Direct labeling by labeling ab's in the Fc region. the wells are coated with antigen and the binding is measured by color change. must have a positive, negative, and control.

Front 13

Western blot

Back 13

HIV example - previous exposure to a pathogen. film with HIV proteins separated by size and charge. if an immune response is present against antigen, then antibodies will bind to them on gel. labeled anti-human immunoglobulins are used to detect the ab's Fc region

Front 14

Autograft

Back 14

one location of body to another

Front 15

Xenograft

Back 15

across specie barriers

Front 16

allograft

Back 16

b/w two members of same species but not identical

Front 17

isograft/syngeneic

Back 17

b/w two identical individuals - twins

Front 18

What is MHC restriction?

Back 18

Tcells have been positively and negatively selected during development to recognize Self HLA and sefl TCR. If an HLA is recognized as non-self then an immune response will be mounted against it.

Front 19

hyperacute rejection

Back 19

occurs within minutes - hours becuase of pre-existing antibodies to donor tissue that activates complements which results in inflammation and ischemia.
Previous antibodies from blood transfusion, pregnancy, prior organ recipient, nonmatching ABO blood type.

Front 20

universal acceptor and donor

Back 20

donor - O
acceptor - AB

Front 21

Microtoxicity testing

Back 21

tests for HLA1 match (HLA - A or B). HLA1's are on CTL's.

Front 22

Mixed lymphocyte reaction

Back 22

used for HLA class II. HLA - DR. if proliferation is noted then they are not compatible.

Front 23

Acute rejection

Back 23

1st week - month due to mismatching HLA antigens. Adaptive immune response.
Direct - seeing donor peptide as nonself which TH1 activate macrophages and CD8T kill trasnplant tissue
Indirect - Recipient Tcells dont directly recognize transplanted cells but recognize cellular material presented by dendritic cells on HLAII as nonself.

Front 24

Chronic rejection

Back 24

months to years after transplant with a reaction against minor histocompability antigens. New dendritic cells continue to present alloantigen and CD4T cells activate Bcells to produce antibodies specific for the donor tissue. Ab's bind donor tissue which recruits macrophages and granulocytes which cause inflammation, ischemia, reconstruction and irreversible damage --> smooth muscle proliferation of intimal layer of blood vessel causes narrowing and ischemia.

Front 25

GVHD; graft-vs-host disease

Back 25

in donor bone marrow, there is a very low level of mature T cells. recipient bone marrow is initially destroyed prior to transplantation and the Tcells from donor go to lymph tissue and initiate an immune response.
high turn over cells - skin rash, jaundice, diarrhea, GI, liver. also against minor histocompability antigens which are self peptides that differ. Minor more because we already halotyped the major.

Front 26

CTLA-4

Back 26

blocks tcell activation by competing CD28 for B7

Front 27

mitotic inhibitors/anti-proliferatives

Back 27

inhibit T-cell proliferation
Azathioprine, cyclophosphamide, methotrexate

Front 28

Macrolides and fungal metabolites

Back 28

inhibit T-cell activation/function
Macrolides – sirolimus (rapamycin), tacrolimus
Fungal – cyclospore

Front 29

Globulins and monoclonal Abs

Back 29

Kill T cells
Globulins – antilymphocyte globulin, antithymoctye globulin
Monoclonal – anti-CD3, anti-IL2 receptor, anti-CD40 ligand

Front 30

Corticosteroids

Back 30

block cytokines/co-stimulatory molecules
iPrednisone, desamethasone

Front 31

IFN alpha/Beta function?

Back 31

Type 1 interferon are secreted by infected cells to warn neighboring cells of infection. upregulate mhcII and inhibits viral replication.

Front 32

Type 1 hypersensitivity

Back 32

immediate response - allergies; requires a previous exposure
IgE and a TH2 response with the cytokines 4,5,13
Mast cells, eosinophils, basophils
Mast cells - drives the reaction, in the mucosal layers and epithelials - ME - release degradative enzymes and inflammation mediators
Eosoniphils - connective tissue - TH2 cells release IL-5 which induces eosinophils --> degranulation and and induction of lipid mediators
Basophils - provide IL-4 to differentiate down TH2 response pathway. found in circulation and in low numbers

Front 33

allergens

Back 33

cause a type I hypersensitivity
effective at low doses
must be proteins to stimulate TH2 response
1st exposure - no rxn - induce B-cell isotype switching to IgE which then binds FceRI on mast cells (if IgE is bound to antigen it wont bind)
on next exposure: it is primed - binding to IgE and activation of mast cells and release of histamines which is immediate and cytokines for secondary response.
also upregulates CD40L and IL-4 to create a larger response through Bcell activation

MOST COMMON DUST MITE PROTEASES

Front 34

Eosinophils and basophils

Back 34

act in the same manner as mast cells but just in different locations, i.e. eosonophils in connective tissue and basophils in the blood.
amplify the response to the allergen

Front 35

mast cell reactions

Back 35

immediate - vasoactive amine release and protease release HISTAMINE - wheel and flare - localized
secondary - prostanglandins, leukotrienes and cytokines. TNF-alpha - tumor necrosis factor = tissue damage - heightened response and spread of inflammation.

Front 36

Atopy

Back 36

genetic predisposition to allergies - not everyone in family has the same allergies because of the different HLA's inherited - more so in the WEST.

Front 37

treatment

Back 37

slowly give increasing doses to allergen which will cause an isotype switch of IgE to IgG.

Front 38

type II sensitivity

Back 38

IgG production against surface protein on cell or extracellular protein. nothing is abnormal. activate complement or ADCC via NK cells. EX: penicillin binding to RBC cell surface. macrophage will present epitope to CD4+ cell which will activate B cell and cause cell lysis upon second exposure.

Front 39

Type III hypersensitivitie

Back 39

IgG against soluble antigen. more antigen intially than antibody, soon the immune complexes form which can activate complement. Immune complexes in tight areas like capillaries causes a lot of injury. If you cannot clear --> mild fever, arthritis, vasculitis, nephritis b/c the immune complexes clog up the small spaces and mess up function. Ex: serum sickness and farmer's lung.

Front 40

Serum sickness

Back 40

before passive immunization. infect animals, bleed animals, and collect antibodies, but the antibodies was horse so the body forms immune response to horse antibody becuase they were unable to clear immune complexes quickly.

Front 41

Type IV sensitivity

Back 41

Tcell driven. two types - delayed type and tcell mediated. delayed type you call in memory T cells that come in a cause the response.

Front 42

Celiac Disease

Back 42

inner lining of small intestine by gluten-derived peptides presented by HLA-DQ2 and DQ8 which are type 2, lose villi which causes diarrhea and cannot absorb food.

Front 43

steven-johnson

Back 43

type 4 and type2 = mixed sloughing of skin.

Front 44

retraction of endothelial

Back 44

venules
induced by histamines, NO, and other mediators
Rapid and short lived

Front 45

Endothelial injury

Back 45

arterioles, caps, and venules
caused by burns or microbial toxins
rapid; maybe long lived

Front 46

leukocyted mediated injury

Back 46

occurs in venules,pulmonary caps
associated with late stages of inflammation
long lived

Front 47

Increased transcytosis

Back 47

venules
induced by VEGF
increase in number/size of cytoplasmic channels

Front 48

rolling and extravasation

Back 48

1. adhesion by 3 mechs
i. p-selectin stored intracellulary in Weibel-Palad bodies in endos are distributed to surface in response to histamine and thrombin
ii. IL-1 and TNF-a induce E-selectin, ICAM-1, VCAM-1
iii. increase affinity by chemokines LFA-1 making integrin high affinity
2. transmigration - involves PECAM-1, psuedopods, and neutrophils
3. chemotaxis
i. exogenous - originating from source like bacterial N-formyl-methionine
ii. endogenous - produced by injured host liek C5a, Leukotriene B4 (LTB4), and IL-8
iii. pseudopod formation and movement by activating Phospholipase C cascade w/induction of intracell Ca+ and cytoskeleton reformation
4. leukocyte activation
i. arachidonic acid
ii. degranulation and release of lyso enzymes
iii. O2 burst
iv. cytokine release
v. increase binding affinity

Front 49

5 signs of inflammation

Back 49

rubor - redness - vasodilation, stasis
tumor - swelling - increase permeability, cellular infiltration
calor - heat - vasodilation, fever
dolor - pain - badykinin, prostaglandins
functio laesa - loss of ucntion

Front 50

vasoactive amines

Back 50

1. histamine - mast cells, basophils, and platelets which
causes vasodilation, permeability, redistribution of P-selectin
Triggers: IgE, injury, anaphylotoxins C3a, C5a and cytokines IL-1

Front 51

complement

Back 51

complement
MAC, anaphylatoxins which stimulate histamine release, C5a which chemotactic, and C3b for opsonization

Front 52

kinin

Back 52

Factor 12 (hageman factor) initiates kinin system producing kallikrein which cleaves kninogen to bradykinin
effects: vasodilation, permeability, pain, bronchoconstriction

Front 53

Clotting

Back 53

Factor 12: produces thrombin, factor 2a, that bind PARS whch redistributes P-selectin, produces prostaglandins, platelet activatin factor and releases NO.

Front 54

arachidonic acid

Back 54

released by phospholipases:
COX: prostaglandins + bradykinin = pain
inhibited by aspirin/NSAIDs
PGI2 - vasodilation and inhibits platelet aggregation
Thromboxane A2 - from platelets - vasoconstriction and promotes platelet aggregation
PGD, PGE, PGF - vasodilation
COX = VASODILATION
LOX = VASOCONSTRICTION
LTB4 - chemotaxis
LTC, D, E - constriction
Lipoxins - chemotaxis/adherence
PAIN = BRADYKININ AND PGE2

Front 55

Transudate

Back 55

fluid only
caused by increase in BP or decrease in proteins/oncotic pressue

Front 56

Exudate

Back 56

increased permeability
fluid/cells/protiens

Front 57

abscesses

Back 57

neutrophils with pus secretes enzymes that cause liquefactive necrosis adn a cavity
boils

Front 58

ulcer

Back 58

sloughing of necrotic tissue

Front 59

outcomes of acute inflammation

Back 59

1. resolution
2. resolution with scarring
3. abscess or ulcer
4. progression to chronic
5. adhesions

Front 60

acute
chronic
granulomatous formation

Back 60

neutrophils
monoblasts --> monocytes --> macrophages = official start of chronic a major cylce that is present:
Th release IFN-g --> activates macrophage --> macrophage releases IL-12 --> activates more Th
Granulomas - focal aggregates of macrophages
1. immune - unable to degrage a phagocytosed substance which forms epitheloid cells --> langhans giant cells --> necrotic center. identify by neuclei on periphery with a rim of plasma cells and fibroblasts
2. foreign body - too large to phagocytose. ident by no rim around it.

Front 61

Autoimmune disease

Back 61

more common in caucasians and females
It is initiated by self-reactive Tcells [CTLs].

Front 62

APECED

Back 62

rare defect in AIRE which causes an autoimmune disorder so they cannot turn on the extra genes that subjects Tcells to a bunch of different self peptides in development for negative selection. they present with candidia, hypoparathyroidism, adrenal failure, diabetes, testicular atrophy.

Front 63

peripheral T cell tolerance

Back 63

anergy:
engagement of self pelptide
1. but lacking APC's costimulatory B7
2. Binding of CTLA-4 to B7
Some Tcells become Tregs during development which
1. can inhibit Tcell activation of Naive Tcells by inducing apoptotic proteins
2. FasL - Fas apoptosis
Tregs are indirect shutting off by CTLA-4 binding to B7

Front 64

Bcell tolerance

Back 64

needs Tcells to be activated and will become anergic after a time or will die b/c it cannot get into lymph nodes. Anergic Bcells downregulate IgM and only expresses IgD and does apoptosis FasL(CD4+) and Fas(Bcell) binding.

Front 65

B27

Back 65

men with ankylosign spondylitis

Front 66

Type ii autoimmune

Back 66

cell-surface moleculel

Front 67

hemolytic anemia

Back 67

IgG and IgM bind to Rh on erythrocytes = anemia

Front 68

Graves disease

Back 68

Anti-TSH antibodies stimulate the TSH receptor resulting in unregulated hyperthyroidism

Front 69

Endocrine glands and autoimmune

Back 69

tissue specific proteins, highly vasularized, and loss of function has wide systemic effects

Front 70

Lupus

Back 70

Type III: immune complexes
butterfly rash
arthritis/fever/vasculitis/fatigue/organ failure kidney, lungs, heart, and nervous tissue

Front 71

type III autoimmunity

Back 71

IgG antibodies against common intracellular components that forms soluble complexes with IgG which deposit in small areas. autoantibodies against everything in the cell.

Front 72

Type IV

Back 72

DM, MS - tcell driven

Front 73

Rheumatoid

Back 73

most common RA, anti-IgG antibodies that recognize IgG. have mixed reactions

Front 74

ms

Back 74

type 4 antibodies against myelin sheaths
visual, muscle weakness, coordination, numbness

Front 75

myasthena gravis

Back 75

autoantibodies against acetylcholine receptors. turns off function. lax in muscles of face - eyes to mouth

Front 76

corticosteroids

Back 76

suppress immune function

Front 77

cyclosporine

Back 77

inhibit Tcell proliferation

Front 78

Tregs

Back 78

foxp3 is found in only tregs and they express foxp3 an dCD25 at high levels.
IL-4, IL-10, TGF-B - enhance TH2 and inhibit TH1
inhibiting rejection of an embryo
miscarriages associated with low levels of Tregs

Front 79

IPEX

Back 79

primary immunodeficiency, disregulation of foxp3 leading to dysfunctional Treg
Triad - watery diarrhea, eczematous dermatitis, and endocrinopathy which is insulin dependent diabetes mellitus

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Th1

Back 80

IFN-g and IL-12

Front 81

TH2

Back 81

IL-4 6,13

Front 82

IFN a and b

Back 82

infected cells screaming fire

Front 83

NK

Back 83

inhibited by MHCi
Activated by IFN-a and IFN-B from virally infected cells, IL-12 from phagocytes, and IFN-g from TH1 cells
kill by granzymes not fas/fasl

Front 84

ADCC

Back 84

opsonization by antibodies then IgG binds Fc of receptor will allow the release of lytic enzymes and worms could be coated will attracted eosinophils

Front 85

anitbody effector functions

Back 85

complement activation
opsonization
inflammation via IgE triggering degranulation of mast cells and basophils
neutralization of microbes and microbial products
ADCC

Front 86

herd immunity

Back 86

immunity acquired when a critical number of people are vaccinated which reduces the transmission of the disease and protects the immunocompromised individuals